Osteoporosis is a growing clinical and public health problem among older men. The greater prevalence of osteoporosis in women and white men has long over-shadowed the importance of this condition in black men. Unfortunately, there remains a widely held misconception that blacks are "protected" from bone loss and osteoporosis such that osteoporosis is underdiagnosed, undertreated and underreported in black men. As the population ages, considerably more black men will develop osteoporosis. Thus, there remains an urgent need to better understand bone loss and osteoporosis in black men so that high-risk men can be better identified for prevention and treatment. The proposed research seeks to better define the natural history and mechanisms underlying age-related bone loss in black men. To address this goal, we are proposing to continue our Tobago Bone Health Study (R01-AR049747), a unique population-based study of bone mineral density (BMD) in 2,424 black men aged e40 years. Men who completed a baseline quantitative computed tomography scan will be invited to complete a second scan, with an average follow-up of 6.6 years. Cortical and trabecular volumetric BMD and bone geometry will be remeasured to characterize the rates and determinants of bone loss. Detailed protocols, extensive training of staff, and well-established quality control procedures will continue to ensure high quality data collection. An extensive database of clinical and epidemiologic factors including anthropometry and body composition, medical conditions, lifestyle characteristics, dietary intake, and use of medications, archived specimens, and state-of-the-art biochemical assays will be used to: 1) describe the natural history of trabecular and cortical bone loss with age;2) identify the lifestyle, medical and anthropometric related risk factors for accelerated trabecular and cortical bone loss with aging;3) test the hypotheses that lower 1,25 dihydroxyvitamin D and 25-hydroxyvitamin D and higher bioactive parathyroid hormone concentrations are each associated with increased rates of trabecular and cortical bone loss with age;4) determine if higher concentrations of pro-inflammatory biomarkers, interleukin-6, tumor necrosis factor alpha and c-reactive protein, are each associated with accelerated loss of trabecular and cortical bone;and 5) evaluate if men with poorer renal function experience greater trabecular and cortical bone loss with aging. The proposed research will have a substantial impact on the field by providing deeper insight into the physiologic and clinical basis for age-related bone loss among black men, a population that has heretofore been significantly under-represented in osteoporosis research. PUBLIC HEALTH RELEVANCE: Osteoporosis is a growing clinical and public health problem among older men of all race and ethnic groups. A greater prevalence of osteoporosis among Caucasians has long over-shadowed the importance of this disease in blacks, particularly among men. Indeed, osteoporosis and its associated fractures are substantially underdiagnosed, undertreated and underreported in black men. Our project is the largest and most comprehensive evaluation of skeletal health in black men and will substantially improve our understanding of bone health and skeletal aging in black men. Our proposal seeks to define the natural history, tempo and patterns of bone loss with aging among black men and to identify physiological and clinical risk factors for accelerated loss.